Pain and its alleviation are some of the most important challenges of modern medicine. During the last several decades a great deal of progress has been made in the design of new medications and methods of their administration. The most popular methods of administering the medication to a patient are oral, topical and intramuscular. Analgesics administered in these ways must have a high degree of specificity, as well as pharmacological properties which guarantee easy penetration of biological barriers such as the skin-circulatory system barrier, the intestine-blood barrier and the brain-blood barrier. Such compounds disperse throughout the organism after application, including the central nervous system, where preferentially they block the transmission of pain stimuli through the spinal cord and the perception of pain in the brain. The arsenal of systemic application techniques of analgesics was enriched in the last few years by modern methods of administering the medication directly to those structures where preferentially it is expected that it would act on the receptors participating in the dampening or generation of pain signals. The medication may be introduced in the form of a physiological saline solution, using a syringe extended with a catheter introduced to the destination site of the medication. The syringe can be replaced with a variety of infusion pumps allowing the constant introduction of the medication over time, and/or allowing the doctor and/or the patient to control the dose of medication administered. Descriptions of the techniques and devices in questions are well presented in the work by D. B. Carr and M. J. Cousins entitled “Spinal route of Analgesia. Opioids and future options”, which is a chapter in “Neuronal blockade in clinical anesthesia and management of pain” (ed. M. J. Cousins and P. O. Bridenbaugh), published by Lippincott-Raven Press, Philadelphia, 1998, pp. 915-983. The chief target of analgesic medication are receptors in the central nervous system, particularly in the spinal cord. In the last years, however, the presence receptors modulating pain stimuli has also been noted at sites of tissue damage. That is why independently of central nervous system analgesia, local application at post-operative sites is also practised. In all these modern medication application techniques traditional analgesic preparations are used, such as morphine or phentanyl. Such compounds are characterised by high biological barrier permeability, thus their efficacy in local application is limited.
In 1986, Andrzej W. Lipkowski was granted Polish Patent No. 131730 for “A Method for the Production of Peptides with Morphine-like Activity”. This patent also describes the synthesis of a compound with the structure presented in FIG. 1. This compound has the common name of biphaline. Investigations of biphaline have shown that this compound has an analgesic activity level similar to morphine when introduced intravenously. Following direct administration to the central nervous system, analgesic activity of the compound was noted, but the level of this activity was variously interpreted by researchers.
The purpose of this invention is to deliver new compounds, which could be utilised to obtain better analgesic agents, particularly for direct local administration, which would at the same time show high anaesthetic activity and were denuded of the known unwanted side effects of opiate compounds, such as the ability to cause respiratory depression.
It was unexpectedly shown that this problem can be solved by the present invention.